Tissue processor

ABSTRACT

A tissue processing system includes a plurality of processing stations. Each processing station includes a plurality of tissue receiving areas that are each configured to accommodate a tissue sample as well as physically isolate that tissue sample from other tissue samples at other receiving areas of the same processing station. Each processing station is configured to separately and individually process the tissue sample at each receiving area to either reduce or eliminate any potential for cross-contamination between the tissue samples undergoing processing at the same processing station. For each receiving area of each processing station, the system is configured to immerse a tissue sample at a particular receiving area in processing fluid for a pre-determined time according to a pre-defined protocol that is based upon parameters of that tissue sample.

CROSS REFERENCE TO RELATED APPLICATION

The application claims priority to U.S. Provisional Patent ApplicationNo. 61/422,772, filed Dec. 14, 2010, the contents of which areincorporated by reference herein in their entirety.

FIELD OF THE INVENTION

The invention is generally directed to a tissue processor and the fieldof histology.

BACKGROUND OF THE INVENTION

A tissue processor automatically performs fixation, dehydration,cleaning, and paraffin impregnation of tissue samples (e.g., livertissue, breast tissue, prostate tissue, etc.). At least two types oftissue processors exist, namely, chamber processors and stationprocessors. A station-type processor includes a plurality of stationsfor processing the tissue samples, which are contained within individualcassettes. An example of a tissue cassette is disclosed in U.S. Pat. No.4,421,246 to Schultz, which is incorporated herein by reference. Thetissue cassettes are loaded into a single basket and taken from onestation to the next station. In a chamber processor, tissue cassettesare loaded in a single enclosed chamber of the processor. The tissuecassettes remain stationary during processing in a fully enclosed retortwhile processing reagents and molten paraffin are moved to and from thechamber in a programmed sequence.

In both types of processors, all samples are immersed in a large reagentpool and cross-contamination of small tissue fragments may occur.Cross-contamination of the samples can skew the results of the tissueanalysis. In view of the foregoing, there is a need to further refinetissue processors in the interests of reducing or eliminating crosscontamination of tissue samples.

SUMMARY OF THE INVENTION

According to one aspect of the invention, a tissue processing systemcomprises a plurality of processing stations. Each processing stationincludes a plurality of tissue receiving areas that are each configuredto accommodate a tissue sample as well as physically isolate that tissuesample from other tissue samples at other receiving areas of the sameprocessing station. Each processing station is also configured toseparately and individually process the tissue sample at each receivingarea to either reduce or eliminate any potential for cross-contaminationbetween the tissue samples undergoing processing at the same processingstation.

According to yet another aspect of the invention, a method ofindividually processing tissue samples using a tissue processing systemincluding a plurality of processing stations includes the steps of (i)receiving information corresponding to parameters of a tissue sample;(ii) positioning the tissue sample in a tissue receiving area of aprocessing station that is physically isolated from a differentreceiving area of the same processing station; (iii) processing thetissue sample according to a pre-defined protocol that is based upon thereceived parameters of the tissue sample; and (iv) transporting thetissue sample to another processing station of the tissue processing forfurther processing.

According to yet another aspect of the invention, a tissue processingsystem includes a first processing station, a second processing station,a plurality of carriers having at least two carrier types, the at leasttwo carrier types including a first carrier configured to receive afirst number of cassettes and a second carrier configured to receive asecond number of cassettes, the first number of cassettes not equal tothe second number of cassettes, a first dispenser for dispensingprocessing fluid in the first processing station and a second dispenserfor dispensing fluid in the second processing station, and a controllerconfigured to control the first and second dispensers to dispense fluidin the first and second processing stations, respectively, based uponreceived information corresponding to parameters of tissue samples thatare docked at those stations.

According to yet another aspect of the invention, a tissue processingmethod includes positioning a tissue processing carrier in a processingstation, the tissue processing carrier including an identifieridentifying a number of cassettes in the tissue processing carrier,identifying the number of cassettes in the carrier, and dispensing fluidin the processing station on each of the identified number of cassettes.

The systems and methods described herein may significantly reduce oreliminate cross contamination of the tissue samples processed by thesame system while providing comparable throughput of the tissue samples.Sample cross contamination may be significantly reduced or eliminate bydispensing processing fluid to individual cassettes that are isolatedfrom one another. Processing fluid cross contamination may besignificantly reduces of eliminated by collecting processing fluidrunoff associated with the dispensing of the processing fluid fordisposal. In accordance with one aspect of the present invention,systems and methods are described that utilize a small amount ofprocessing fluid per cassette. This allows economical processing of thecassettes without the need to reuse fluids.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 depicts a schematic view of a tissue processing system forprocessing a tray of tissue samples, according to an exemplaryembodiment of the invention.

FIG. 2A depicts a schematic view of a tissue processing system forprocessing individual tissue samples, according to another exemplaryembodiment of the invention.

FIG. 2B depicts a cross-sectional view of a tissue cassette positionedin a cassette carrier that is docked at a cassette carrier location of aprocession station.

FIGS. 3A, 3B, and 3C depict a flowchart of exemplary steps for addingcarriers to a tissue processing systems according to an aspect of thepresent invention.

FIG. 4A depicts a tissue processing cassette icon;

FIG. 4B depicts a fluid dispenser icon;

FIG. 4C depicts a plurality of tissue processing carrier icons forcarrying different numbers of cassette(s) (e.g., 1-4 cassettes) inaccordance with an aspect of the present invention; and

FIG. 5 depicts a tissue processing flow for processing carriersincluding different numbers of cassettes in accordance with aspects ofthe present invention.

DETAILED DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 depicts a schematic view of a tissue processing system 10 (alsoreferred to as a tissue processor) for processing a tray of tissuesamples, according to an exemplary embodiment of the invention. Theprocessor 10 disclosed in FIG. 1 is capable of processing tissuessamples from multiple patients without introducing cross-contaminationof the sample fragments or cross-contamination of reagents.

In this exemplary embodiment, each tissue sample (e.g., liver tissue,breast tissue, prostate tissue, etc.) is contained within a tissuecassette 12, and one or more cassettes 12 are positioned on a cassettetray/carrier 16. The cassette tray 16 includes a plurality of cassettereceiving locations 13, each of which are sized to accommodate a tissuecassette 14. The cassette tray 16 defines an enclosed region forimmersing the cassettes 14 in processing fluid (e.g., reagent orparaffin). The cassette trays 16 are preferably available in differentsizes to accommodate different numbers of cassettes 14 (i.e., one traymay accommodate one cassette 14, whereas another tray may accommodatefive cassettes 14). Thus, an operator may select one tray 16 foraccommodating three cassettes 14, and a different tray 16 foraccommodating ten cassettes 14.

The tissue processing system of FIG. 1 includes six stations (labeledStation 1 through Station 6) for processing one or more trays 16carrying one or more tissue cassettes 14 (each cassette containing oneor more tissue samples). According to the exemplary embodiment shown inFIG. 1, station 1 is a load station onto which a cassette tray 16 isloaded, stations 2-4 are reagent stations for processing the tissuesamples within the tissue cassettes 14 of the tray 16, station 5 is aparaffin embedding station for embedding the cassettes 14 withinparaffin, and station 6 is an unloading station. Those skilled in theart will recognize that the number of stations and the functionality ofeach station may differ from that described herein without departingfrom the spirit or scope of the invention. For example, according to analternative exemplary embodiment, station 5 is a reagent station andstation 6 includes an attachment mechanism for attaching an automatedembedding system. As yet another alternative embodiment, station 6 maybe a chilling station.

Referring still to the embodiment of FIG. 1, stations 1-6 each includesa base platform 18 with multiple cassette receiving locations 13 (eightin the illustrated embodiment) for receiving individual cassettes.Stations 2-5 each includes one or more fluid dispensers 22 fordispensing fluid (such as reagent or paraffin) into the tray 16 that ispositioned on the base platform 18 in a particular location of aparticular station, and a drain (not shown) through which the fluid maybe expelled, when desired. In an exemplary embodiment, each station 2-5is able to maintain a desired temperature of the tray 16, develop vacuumat the station (as needed per processing protocol requirements), developpressure at the station (as needed per processing protocolrequirements), and agitate the contents of the tray 16.

The mechanism for agitating the contents of the tray 16 may be amagnetic stirrer, for example. A magnetic stirrer employs a rotatingmagnetic field to cause a stir bar immersed in a liquid to spin, thusstirring it. The rotating field may be created either by a rotatingmagnet or a set of stationary electromagnets, placed beneath the tray.Alternatively, a circular track having different elevations may bepositioned under one or more of the trays 16. As the tray 16 rotates,the different elevations cause the tray 16 to wobble, thereby agitatingliquid within the tray 16. In yet alternative embodiment, the trays 16may be agitated with ultrasonic energy or microwave energy in a mannerthat will be understood by one of skill in the art from the descriptionherein.

To facilitate processing of the trays 16, the tissue processing system10 includes a man-machine interface 24 to enable an operator to enterthe parameters of each cassette tray, a transport mechanism 26 thattransports the cassette trays between the stations, and a processor 25 afor processing computer program instructions stored in a memory 25 b(such as a non-transitory computer readable medium) to operate thestations and the transport mechanism 26 of the system according to apre-defined protocol.

The man-machine interface 24 may include a keypad, a touch screen,and/or a bar code reader, to enable an operator to enter the parametersof each cassette tray 16. The parameters may include the number ofcassettes 14 that are loaded on a particular tray 16, the type of tissue(e.g., liver tissue, breast tissue, prostate tissue, etc.) and the sizeor thickness of the tissue sample that is contained within each tissuecassette. Different tissues require different processing protocols.Based upon these parameters, the computer determines the appropriateprotocol for processing that particular tray 16 of cassettes 14. By wayof example, the protocol for processing a tray 16 of six cassettes 14containing breast tissue may be 4 minutes at station 2 using 10 mL offixative solution, 6 minutes at station 3 using 15 mL of dehydrantsolution, 5 minutes at station 4 using 8 mL of clearant solution and 2minutes at station 5 using 20 mL of paraffin. The foregoing valuesprovided herein are exemplary.

The transport mechanism 26 comprises a mechanism that is capable ofmoving a tray between the various stations 1-6. The transport mechanismmay be a single mechanism or multiple mechanisms translatable along X, Yand/or Z axes and rotatable about X, Y and/or Z axes to move a tray 16between the various stations. In one embodiment, the transport mechanism26 may comprise five independent transport mechanisms, each of which ispositioned between respective adjacent stations to accomplish movementfrom one station to an adjacent station. The transport mechanism 26 maycomprise any combination of a motor, belt, pulley, gear, arm, track, andspring, for example.

For example, the transport mechanism 26 may be a conventional roboticswing arm having gripping arms for grasping an individual cassette 14,an entire tray 16, and/or an individual cassette carrier (described withreference to FIG. 2), and transporting the cassette, tray and/or carrierbetween the processing stations 1-6.

The base platform 18 of each station 1-6 may optionally be translatablealong X, Y and/or Z axes and rotatable about X, Y and/or Z axes formovement in concert with the transport mechanism 26. The stations 1-6may be arranged in a row, or a semi-circle pattern (as shown in FIG. 1).The stations 1-6 may at least partially be enclosed by a fume hoodincorporating a fume extraction fan for removing fumes.

According to one exemplary use of the tissue processor of FIG. 1, thetissue samples which are loaded on an individual tray 16 are preferablyharvested from the same patient to eliminate cross-contamination betweendifferent patients. The cassettes 14 that are loaded on an individualtray 16 may optionally include the same tissue type (e.g., breasttissue). The operator first identifies the type of the tissue sample,the tissue sample size and/or thickness, and the number of cassettes 14that are loaded in the sample tray 16. This information may be inputtedinto the system 10 via the man-machine interface 24. Based on the sampletype, sample size, and number of cassettes 14 entered by the operator ofthe system 10, the system 10 generates the processing protocol for everystation 1-6 that the tray 16 visits.

The processing protocol for each station 1-6 includes, for example, theprocessing time for each station and the volume of processing fluid(e.g., reagent or paraffin) that is to be dispensed at each station. Thetemperature level, the vacuum level and agitation at each processingstation depends upon the of the processing station, i.e., the type ofreagent or paraffin that is used at that station. The operator mayprogram each station 1-6 to perform a specific processing task (e.g.,establish station 1 as a fixative station and establish station 2 as aparaffin) via the man-machine interface 24 or each station 1-6 may bepermanently dedicated for performing a specific processing task (e.g.,station 1 is always a fixative station). The system is pre-programmed toset the temperature level, set the vacuum level and apply agitation ateach station 1-6 depending upon the function of each station 1-6.

The operator then places the tray 16 on the base platform 18 of station1. A sensor may be positioned on or adjacent the base platform ofstation 1 to sense the presence of the newly added tray at station 1.The sensor may be a pressure sensor, an optical sensor or a positionsensor. The transport mechanism 26 of the system transports the tray 16from station 1 to station 2. The reagent dispensers at station 2dispense the pre-programmed amount of reagent into the tray 16,according to the parameters that were initially entered by the operator.The station 2 then agitates, e.g., gently rocks, the tray 16 whilemaintaining the temperature of the tray 16 and the level of vacuumapplied to the tray 16 at the pre-programmed levels. Once thepre-programmed time has expired, the system 10 empties the reagent fromthe tray 16 into a waste container (not shown). The system 10 calculatesthe quantity of reagent (or paraffin) that is contained within the wastecontainer, and prompts the operator to empty or replace the wastereceptacle at the proper time. The various reagent waste streams areaccumulated and recycled separately.

It is possible to program the system 10 such that it applies a reagentto the tray 16 for a fixed period of time, discards the reagent at theend of the period and then refills the tray 16 with fresh reagent againfor another preprogrammed time. This process can be repeated multipletimes, if so desired.

Once processing of the tray 16 at station 2 is complete, the transportmechanism 26 of the system transports the tray 16 from station 2 tostation 3 for further processing. Once processing at station 3 iscomplete, the transport mechanism 26 of the system 10 transports thetray 16 from station 3 to station 4 for further processing. It should beunderstood that the description of the processing steps occurring atstation 2 also apply to stations 3 and 4. According to one exemplaryembodiment, station 2 is a fixative reagent station in which the tissuesare immersed in a fixative solution (e.g., formalin), station 3 is adehydrant reagent station in which the tissues are immersed in adehydrant solution (e.g., alcohol), and station 4 is a clearant reagentstation in which the tissues are immersed in a clearant solution (e.g.,xylene).

Once processing of the tray 16 at station 4 is complete, the transportmechanism 26 of the system 10 transports the tray 16 from station 4 tostation 5 for further paraffin embedding. At station 5, the station 5delivers paraffin into the tray 16 to immerse the cassettes 14 in aparaffin bath. Once processing at station 5 is complete, the transportmechanism 26 of the system transports the tray 14 from station 5 to theunload station 6.

When the tray 16 arrives at the unload station 6, the system prompts theoperator, either visually or audibly, to remove the processed tray 16from the unload station 6. A sensor may be positioned on or adjacent thebase platform of station 6 to sense the presence of the processed tray16 at the unload station 6 after prompting. The sensor may be a pressuresensor, an optical sensor or a position sensor. If the sensor sensesthat the processed tray 16 has not been removed from station 6, thesystem 10 may be configured to prevent another processed tray 16 fromadvancing to station 6. Alternatively, the base platform 18 of station 6may be configured to accommodate multiple trays. It should be understoodthat the functionality of each station 1-6 may vary from that describedherein without departing from the scope or spirit of the invention.

The system is capable of processing multiple trays 16 simultaneously,i.e., processing one tray 16 at station 2, processing another tray 16 atstation 3, and so forth, such that trays 16 may simultaneously undergoprocessing at each station. Simultaneous processing of multiple trays 16results in faster turnaround time. To process multiple trays 16simultaneously, the operator first informs the system 10 that a newlyadded sample tray 16 is waiting for processing by entering theparameters of the newly added tray 16 via the man-machine interface 24(as described previously) and placing that new sample tray 16 at station1. Based on the pre-programmed processing times for the newly added tray16 and the pre-programmed processing times for the trays 16 which areundergoing processing at one or more stations 1-6 of the system 10, thetransport mechanism 26 transports the newly added tray 16 to station 2at the proper moment in time. The timing aspect of the process will bedescribed next.

Because a delay in transporting a tissue sample from one station to thenext station could have an adverse impact upon the processing of thattissue sample, the newly added tray 16 is moved to station 2 at themoment when the newly added tray 16 can advance from station to stationwithout delay caused by the processing of another tray 16 at a laterstation. In other words, even though station 2 may be ready to receivethe newly added tray 16, the system is configured to transport the newlyadded tray 16 to station 2 only when the newly added tray 16 can proceedthrough all of the stations without delay caused by a tray at stations3-6.

FIG. 2A depicts a schematic view of a tissue processing system 50 thatis configured for individualized processing of tissue samples that arepositioned on a processing station, according to another exemplaryembodiment of the invention. The tissue processing system 50 of FIG. 2Ais similar to the tissue processing system of FIG. 1, and only thedifferences between those tissue processing systems are describedhereinafter.

In the system of FIG. 2A, each tissue cassette 52 is positioned in acassette carrier 54 and each station 1-6 includes a plurality ofcassette carrier locations 56 (also referred to herein as tissuereceiving areas) that are each sized to accommodate a single cassettecarrier 54. Thus, each station 1-6 can accommodate multiple cassettecarriers 54. As shown in FIG. 2B, each tissue cassette 52 is positionedin a cassette carrier 54 and each cassette carrier 54 is docked at acassette carrier location 56 of a station.

Each cassette carrier 54 accommodates one cassette 52 (unlike the tray16 of FIG. 1 which accommodates multiple cassettes). The cassettecarrier 54 is sized to contain a single tissue cassette 52 and is largeenough to accommodate a limited volume of fluid, such as reagent orparaffin, into which the cassette 52 is immersed. The cassette carriers54 are self-contained units that are physically isolated from each otheron cassette carrier locations 56 of the base platform 58 of a station1-6 to eliminate the potential for cross-contamination of the tissuesamples on the same station. The tissue samples at any particularstation 1-6 of the system 50 of FIG. 2 may be harvested from differentpatients without exposing the tissue samples at any station tocross-contamination.

The stations 2-5 of the system 50 are each configured for individualizedprocessing of the cassettes 52 that are positioned at the cassettecarrier locations 56 of each station 2-5. More specifically, eachprocessing station 2-5 is capable of delivering fluid (e.g., reagent orparaffin) into a single cassette carrier 54 without delivering thatfluid into another cassette carrier 54 that is also positioned on thesame station. Each station 2-5 is capable of discarding the fluid in asingle cassette carrier 54, as opposed to discarding the fluid in all ofthe cassette carriers 54 on the same station at the same time. Eachstation 2-5 is also capable of agitating individual cassette carriers54, as opposed to agitating all of the cassette carriers 54 that arepositioned on the same station 2-5 at the same time. Each station 2-5 iscapable of controlling the temperature of the individual cassettecarriers 54.

According to one exemplary use of the tissue processor of FIG. 2, theoperator first identifies the type of the tissue sample that iscontained within a cassette carrier 54. This information is input intothe system via the man-machine interface 60 of the system 50. Based onthe sample type and sample size entered by the operator of the system50, the system 50 automatically generates the protocols for thatcassette carrier 54 at each station 2-5. The protocols include at leastthe following for each station 2-5 of the system: the cassette carrierlocations 56 into which the cassette carrier 54 will be delivered, thepre-programmed time, the temperature level, the vacuum level, and/or thequantity of reagent or paraffin to be dispensed.

The operator then places the cassette carrier 54 into a cassette carrierlocation 56 (also referred to as a tissue receiving area) on the baseplatform 58 of station 1. The transport mechanism 62 of the system 50transports the cassette carrier 54 from a cassette carrier location 56at station 1 to a pre-determined cassette carrier location 56 at station2. Movement of the cassette carrier 54 from station 1 to station 2 maybe accomplished by virtue of the transport mechanism 62 as well asrotation of the base platforms 58 of station 1 and/or station 2. Thesystem is configured to remember the particular cassette carrier 54location of station 2 in which the cassette carrier 54 is positioned.

The system then rotates the base platform 58 of station 2 to align thecassette carrier 54 with the fluid dispenser 64 of station 2. The fluiddispenser 64 at station 2 dispenses the pre-programmed amount of reagent(or any other fluid) into the cassette carrier 54, according to theparameters that were initially entered by the operator. The station 2then agitates, e.g., gently rocks, the cassette carrier 54 whilemaintaining the temperature of the cassette carrier 54 and the level ofvacuum applied to the cassette carrier 54 at the pre-programmed levels.Once the pre-programmed time has expired, the system tilts the cassettecarrier 54 to discard the reagent into a waste container (not shown).Depending upon the protocol associated with the cassette carrier 54, thesystem 50 may be configured refill the cassette carrier 54 with freshreagent again for another preprogrammed time. This process can berepeated multiple times. It should be understood that the cassettecarrier 54 can undergo all of the above-described steps withoutimpacting the processing of other cassette carriers 54 at station 2.

Once processing at station 2 is complete, the transport mechanism 62 ofthe system 50 then transports the cassette carrier 54 from station 2into a pre-determined cassette carrier location 56 at station 3 forfurther processing. Once processing at station 3 is complete, thetransport mechanism 62 of the system then transports the cassettecarrier 54 from station 3 into a pre-determined cassette carrierlocation 56 at station 4 for further processing. Once processing atstation 4 is complete, the transport mechanism 62 of the system 50 thentransports the cassette carrier 54 from station 4 into a pre-determinedcassette carrier location 56 at station 5 for further processing. Itshould be understood that processing steps described with reference tostation 2 also apply to stations 3-5.

Once processing at station 5 is complete, the transport mechanism 62 ofthe system 50 transports the cassette carrier 54 from station 5 to apre-determined cassette carrier location 56 at unload station 6. Whenthe cassette carrier 54 arrives at station 6, the system 50 prompts theoperator, either visually or audibly, to remove the processed cassettecarrier 54 from the unload station 6. A sensor 70 may be positioned onor adjacent the base platform 56 of the unload station 6 to sense thepresence of the processed cassette carrier 54 at the unload station 6.If the sensor 70 senses that the processed cassette carrier 54 has notbeen removed from station 6 by the operator, the system 50 may beconfigured to prevent another processed cassette carrier 54 from movingto station 6. Alternatively, the base platform 18 of station 6 may beconfigured to accommodate multiple cassette carriers (as shown in FIG.2).

The system 50 is capable of individualized processing of multiplecassette carriers 54 at multiple stations 2-5. For example, threecassette carriers 54 can simultaneously undergo processing at station 2,while five cassette carriers 54 simultaneously undergo processing atstation 3, and so forth. Individualized processing of multiple cassettecarriers 54 at multiple stations 2-5 results in faster turnaround timeof the tissue samples.

The system 50 employs an algorithm for simultaneously processingmultiple cassette carries 54 at multiple stations 2-5. Because delayingthe transport of a tissue sample from one station to the next stationcould adversely impact the processing of that tissue sample, a newlyadded cassette carrier 54 at station 1 is only moved to station 2 at themoment when the newly added cassette carrier 54 can advance from stationto station without delay caused by the processing of another cassettecarrier 54 at a downstream station. Using the algorithm, the system 50determines the moment at which the newly added cassette carrier 54 movesfrom station 1 to a predetermined cassette carrier location 56 ofstation 2 as a function of (i) the processing protocol for the newlyadded cassette carrier 54, (ii) the number of available cassette carrierlocations 56 at each station, and (iii) the processing protocol for thecassette carriers 54 which are undergoing processing at downstreamstations of the system (i.e., stations 2-5). In other words, even thougha cassette carrier location 56 at station 2 may be available to receivethe newly added cassette carrier 54, the system 50 will transport thenewly added cassette carrier 54 to its predetermined cassette carrierlocation 56 at station 2 only when the newly added cassette carrier 54can proceed through all of the stations without delay caused by anothercassette carrier 54 undergoing processing at any of stations 3-6.

FIGS. 3A, 3B, and 3C depict a flowchart of exemplary steps forscheduling/adding carriers to a tissue processing systems according toan aspect of the present invention. At decision block 100 of FIG. 3A,the system asks whether any sample carriers are being processed. Ifthere is no sample carrier being processed, a new sample carrier'sprocessing can start right away (i.e., go to ‘B’ in FIG. 3C). Once asample carrier is scheduled to be processed, the Stop and Start Timesfor each Processing Station (PS) are calculated by the software inaccordance with the equations 202, 204, 206 and 208 shown in FIG. 3C andretained in the memory.

When a next Sample Carrier is being loaded in the system, and the answerto decision block 100 of FIG. 3B is ‘Yes’, the software calculates theprocessing time at various stations based on the sample type andthickness. These processing times at various stations are used tocalculate if a processing station will be done processing previouslyscheduled sample carriers when it is required to process this new samplecarrier. More particularly, at decision blocks 102 a-102 d, each stationis checked to determine whether a processing station will be doneprocessing previously scheduled sample carriers when it is required toprocess this new sample carrier.

For each station, if a processing station will not be finishedprocessing other sample carrier(s), the start of the processing of thenew sample carrier is delayed according to equations 104 a-104 d. Thecalculated delay time for each processing station is added to theprocessing station 1 Start Time in accordance with equation 101. Onceall four processing stations are available, the new sample carrier isscheduled for processing and the processing station availability times(Process Station Stop Time) are updated according to equations 106 a-106d. The Process Station Start Times are then updated according toequations 108 b-108 d. It should be noted that the processing times atrespective stations are derived as the Station Time for processing thetissue based on the sample type and thickness and the time to transportthe sample is added to the processing time.

For an expanded system with multiple sample carrier capacity at eachstation, the software for the expanded system will be more complexcompared to the software for single sample carrier processing at eachstation. Multiple levels of complexities can be added as describedbelow.

-   -   (a) Basic System: A system that will schedule one sample carrier        at a time as it is loaded to ensure that the firs sample carrier        loaded in will start the processing first.    -   (b) Optimized System: A system that can optimize the throughput        of the processed sample carriers once some are already being        processed to see if by starting processing of a sample carrier        that was loaded later can actually be processed sooner by        delaying the start of some other slide carrier.    -   (c) Flexible time optimized system: A system that may be        programmed by the user to specify the flexibility of some        processing times (e.g. longer formalin time at station 1 is okay        or time at each station can be extended by a few seconds, etc.)        to improve the overall throughput.    -   (d) A system with more than one reagent dispenser at a given        station: This system will have additional facility to remember        when to discard the first reagent and add the next reagent        within the station for a given sample carrier.

The scheme for the basic system forms the basis for the other twoversions. This scheme follows the logic described above with more “housekeeping” requirements at each process station.

Processing at each station may be as follows:

1. Initialize:

-   -   a. set all positions as empty by setting the Stop Time for each        position equal to the Current Time;    -   b. set Station Stop Time equal to the Current Time; this        variable identifies that there is at least one position is        available for accepting a new Sample Carrier;

2. Scheduling a Sample Carrier:

-   -   a. Check if the Station Stop Time is less than or equal to the        Current Time.        -   i. if it is, this indicates that at least one position is            available at this Processing Station.        -   ii. identify which position is available by checking the            Stop Time for each position and the one with the earliest            Stop Time is the one to allocate.        -   iii. store the position number to be allocated and return            the message that a position is available.    -   b. if the station is not available, find out the earliest Stop        Time. Store position number and set the Delay Time equals        earliest Stop Time minus Current Time. Return the message that        there are no positions available and a delay equals Delay Time        will make one position available.

3. Once all processing stations report that a position will be availablefor the sample carrier if it started with the maximum required delay,each station will set up the Stop Time for the available position equalsthe Final Start Time for that station plus the Processing Time at thatstation.

4. When the Stop Time for a given position equals the Current Time, theprocessing for that sample carrier is completed and it needs to move tothe next processing station. No further housekeeping for the positionstatus will be necessary.

FIG. 4A depicts a tissue processing cassette icon 80 and FIG. 4B depictsa fluid dispenser icon 82. FIG. 4C depicts a plurality of tissueprocessing carrier icons 84 a through 84 d (referred to collectively astissue processing carriers 84 or sample carriers 84 and generally astissue processing carrier 84) for carrying different numbers ofcassette(s) 80 (e.g., 1-4 cassettes) in accordance with an aspect of thepresent invention.

FIG. 5 depicts an alternative exemplary tissue processing system flow 88for processing trays/carriers including different numbers of cassettesin accordance with aspects of the present invention. Different carriersare designed to carry a different number of cassettes. In an exemplaryembodiment, each carrier includes one or more cavity(ies), with eachcavity holding a cassette and providing some additional volume aroundand below each cassette that it is designed to hold. The system 88allows each carrier to hold a different amount of reagent that willsurround each cassette placed in it. Thus, a carrier that holds fourcassettes will hold four times as much reagent volume as the reagentheld by a carrier that holds only one cassette.

Each carrier can have a feature (for example a different hole pattern ina corner, or a bar code) to identify the number of cassette(s) and,optionally, their placement within the carrier.

The benefits of the system:

1. No reagent cross contamination since the fresh reagents may alwaysused.

2. No sample cross contamination since the samples are never batched inaccordance with one embodiment.

3. No over processing or under processing since each sample can beprocessed based on the most appropriate time durations based on thesample type and thickness as specified by the user.

A transport mechanism and a controller are not shown in the figure tofacilitate depiction. The transport mechanism may include a conveyor forconveying the carriers from one processing station to the next.

The system 88 depicted in FIG. 5 shows multiple (i.e., six)stations—i.e., one load station 90, four processing stations (PS 1, PS2, PS 3 and PS 4), and one unload station 92. Exemplaryfeatures/characteristics of each station in accordance with an exemplaryembodiment are described below.

Load Station 90:

The operator may load one tissue processing carrier 84 at a time at theload station 90. The carrier 84 may have one or more cassettes 80. Inthe event there are more than one cassette 80 in a carrier 84, in anexemplary embodiment each cassette 80 in the carrier 84 will includesample from the same organ of the same patient having the samethickness. The carrier 84 may have a bar code that describes the detailsof the sample (e.g. ID, sample type and thickness). The load station 90will detect a new sample carrier 84 being loaded by the operator andwill prompt the user to enter the details of the sample. Alternatively,it can be equipped with a bar code reader that identifies the sampleinformation automatically.

The load station 90 may have sufficient storage space for more than onesample carrier 84 and means to transport the sample carrier 84 from oneposition to the next (for example a conveyer or a carousel) until thesample carrier 84 is transported to the first processing station (PS1).

The system software decides when the processing for the sample canbegin. Once the start time for the processing is reached, the systemwill move the sample from the Load Station to the first processingstation, PS1.

In an exemplary embodiment, the system can process sample carriers 84with different combinations of different number of cassettes 80,different types of sample and samples of different thicknesssimultaneously.

Processing Station (PS1 through PS4):

Each processing station PS1-PS4 may have one or more reagent dispensers82. Each processing station PS1-PS4 will dispense one type of reagent.Typically, reagent dispensers at PS1 will have a fixative (e.g.formalin), at PS2 it will have a dehydrant (e.g. alcohol), at PS3 itwill have a clearant (e.g. xylene) and at PS4 it will have the embeddingmedia (e.g. paraffin). In an exemplary embodiment, one or more of theprocessing station (e.g., all) can develop vacuum inside the stationPS1-PS4 if required for processing the tissue, maintain a desiredtemperature for processing the tissue, and/or provide agitation to thesample carrier 84 for better mixing of the sample with the reagent forimproved processing. Alternate means of mixing may include usingultrasonic energy or using microwave energy.

The system will determine the amount of reagent to be dispensed based onthe number of samples/cassettes 80 and also based on the pre-determinedreagent quantity to be dispensed per sample. For example, the system mayhave been programmed to dispense 5 ml of reagent at PS1 for every sampleand if a sample carrier with 3 cassettes is being processed, the systemwilt dispense 15 ml of reagent.

A processing station PS1-PS4 may have more than one reagent dispenser 82to dispense same type of reagent but of different concentration. Forexample at PS 2, there may be three dispensers one for 50% alcohol, onewith 80% alcohol and a third one with 100% alcohol.

Once the processing time for the given reagent for a specific type andthickness of the sample is over, the system will collect the reagentfrom the sample carrier in a waste collector at the processing station,e.g., to eliminate the possibility of fluid cross contamination. Thecollected reagent may then be refined, recycled for re-use, ordiscarded. In contrast, many conventional systems automaticallyredistribute recycled reagent to the various stations, which cancross-contaminate the tissue samples at those stations.

If the processing station PS1-PS4 has only one reagent dispenser 82, thesample carrier 84 is taken to the next processing station. For a systemwith more than one reagent station, a subsequent reagent dispenser 82dispenses the next reagent at the same processing station until everyreagent has been dispensed and mixed with the sample once. At the end ofmixing with the last reagent, the sample carrier 84 will be transportedto the next processing station.

In an exemplary embodiment, the user will have an option to decide ifthe last reagent (typically paraffin) at the last station (PS4) will bediscarded or not before transporting the Sample carrier to the UnloadStation.

Unload Station 92:

Unload station 92 may be a temperature controlled station. This stationwill continue to collect the sample carriers 84 as their processing iscompleted at PS4. This station will alert the user when the sample isready for pick up. The system will not transfer any more samples fromPS4 to the unload station 92 if there is no more room to hold one moresample.

Processing Method:

A sample carrier 84 with a known number of cassettes is loaded at theload station 90 by the operator. The operator enters the number ofcassettes 80, and the information about the sample. This information caninclude the sample ID, type of sample (e.g. prostate, breast, brain,etc.) and the thickness of the sample (e.g. 2 mm, 3 mm, etc.).Alternatively, a bar code applied to the carrier 84 may contain the sameinformation and the system will read that information from the bar code.

Based on the sample type, the thickness of the sample(s) and the numberof cassettes 80, the system 88 decides the processing time and thequantity of processing fluid that is required at each of the processingstations. These processing parameters may have been entered by the userprior to loading samples or may have been programmed at the factory andmay have been subsequently modified by the operator. For example, asample carrier 84 with one 2 mm prostate sample cassette 80 may receive5 ml of reagent, one with two cassettes 80 may receive 8 ml, and onewith three cassettes 80 may receive 11 ml.

Next, the system 88 calculates the start time for processing the samplesuch that each of the Processing Stations PS1-PS4 will be available whenneeded. An algorithm to perform this calculation is described above.

Although this invention has been described with reference to particularembodiments, it will be appreciated that many variations may be resortedto without departing from the spirit and scope of this invention. Forexample, the number of stations and the functionality of each stationmay vary from that described herein without departing from the scope andthe spirit of the invention.

What is claimed:
 1. A tissue processing system comprising: a plurality of processing stations, wherein each processing station includes a plurality of tissue receiving areas that are each configured to accommodate a tissue sample as well as physically isolate that tissue sample from other tissue samples at other receiving areas of the same processing station, wherein each processing station is configured to separately and individually process The tissue sample at each receiving area to either reduce or eliminate any potential for cross-contamination between the tissue samples undergoing processing at the same processing station, wherein at least two stations of the plurality of processing stations are reagent stations that have a fluid dispenser to dispense fluid onto the tissue samples, and a heater to heat the tissue samples, and each station is configured to expose the tissue samples to vacuum pressure, and agitate the tissue samples at that station, a robotic arm for transporting the tissue samples between the processing stations, wherein each processing station includes a rotatable base platform that is configured to rotate in concert with movement of the robotic arm, and the system is configured to rotate each rotatable base platform to align a tissue sample with a fluid dispenser to dispense either reagent or paraffin directly onto the aligned tissue sample, and wherein the robotic arm is configured to transport only one tissue sample of a plurality of tissue samples that are positioned at the rotatable base platform of one of the plurality of processing stations to another rotatable base platform of another one of the plurality of processing stations for further processing at the another one of the plurality of processing stations.
 2. The tissue processing system of claim 1, wherein each of the tissue samples is positioned within a respective cassette that is positioned within a particular tissue receiving area of the processing station.
 3. The tissue processing system of claim 1, wherein each of the tissue samples is positioned within a respective cassette, and the cassette is positioned within a cassette carrier that is positioned within a particular tissue receiving area of the processing station.
 4. The tissue processing system of claim 1, wherein at each receiving area of each processing station, the system is configured to immerse a tissue sample in processing fluid for a pre-determined time according to a pre-defined protocol that is based upon parameters of that tissue sample, wherein, the pre-determined time for processing one tissue sample at a given processing station can differ from the pre-determined time for processing another tissue sample at the same processing station.
 5. The tissue processing system of claim 1 further comprising a non-transitory computer readable medium including computer program instructions causing a general purpose computer of the system to operate the individual processing stations of the system according to a pre-defined protocol.
 6. The tissue processing system of claim 5, wherein the protocol of a particular processing station is defined on the basis of parameters of the tissue that is positioned at each receiving area of the particular processing station.
 7. The tissue processing system of claim 5, wherein the protocol of the entire system is defined on the basis of parameters of the tissue that is positioned at each receiving area of each processing station.
 8. The tissue processing system of claim 5 further comprising a man-machine interface configured for transmitting data corresponding to a type of tissue of a particular tissue sample and a size of the particular tissue sample to the general purpose computer.
 9. The tissue processing system of claim 1, wherein each processing station is configured to process the tissues samples at the receiving areas for different periods of time and different vacuum and pressure levels.
 10. A tissue processing system comprising: a plurality of processing stations, wherein each processing station includes a plurality of tissue receiving areas that are each configured to accommodate a tissue sample as well as physically isolate that tissue sample from other tissue samples at other receiving areas of the same processing station, wherein each processing station is configured to separately and individually process the tissue sample at each receiving area to either reduce or eliminate any potential for cross-contamination between the tissue samples undergoing processing at the same processing station, wherein at least two stations of the plurality of processing stations are reagent stations that are each configured to dispense fluid onto the tissue samples, heat the tissue samples, expose the tissue samples to vacuum pressure, and agitate the tissue samples at that station, a robotic arm for transporting the tissue samples between the processing stations, wherein each processing station includes a rotatable base platform that is configured to rotate in concert with movement of the robotic arm, and the system is configured to rotate each rotatable base platform to align a tissue sample with a fluid dispenser to dispense either reagent or paraffin directly onto the aligned tissue sample, and wherein the robotic arm is configured to transport only one tissue sample of a plurality of tissue samples that are positioned at the rotatable base platform of one of the plurality of processing stations to another rotatable base platform of another one of the plurality of processing stations for further processing at the another one of the plurality of processing stations, a first dispenser for dispensing processing fluid in a first processing station of the plurality of processing stations and a second dispenser for dispensing fluid in a second processing station of the plurality of processing stations, each dispenser for immersing tissue samples in the carriers at those stations in the processing fluid; and a controller that is configured to control the dispensers, wherein, based upon received information corresponding to parameters of tissue samples the controller is configured to control the first and second dispensers to dispense a quantity of processing fluid in the first and second processing stations, respectively.
 11. The tissue processing system of claim 10, further comprising: a plurality of carriers having at least two carrier types, the at least two carrier types including a first carrier configured to receive a first number of cassettes and a second carrier configured to receive a second number of cassettes, the first number of cassettes not equal to the second number of cassettes; wherein the controller is configured to control the first and second dispensers to dispense a quantity of processing fluid in the first and second processing stations, respectively, based on the number of cassettes in the first and second processing stations, the type of tissue samples within the cassettes and the size of the tissue samples within the cassettes.
 12. The tissue processing system of claim 10, further comprising: at least one vessel configured to collect fluid runoff associated with the fluid dispensed from at least one of the first or second fluid dispensers to eliminate fluid cross contamination. 